Exam 1: Virology I Flashcards

1
Q

Virus

A

Nucleic acid surrounded by a protein coat = nucleic capsid
Not living organisms but either have DNA or RNA, not both
Obligate intracellularparasites: cannot produce energy, no metabolism, no reproduction, etc.
Naked viruses or have a nuclear envelop (membrane) from the host
Viruses are unable to make energy, synthesize their own proteins, or replicate their genome independently of host cells

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2
Q

Viral Properties vs. Cell

A

Nucleic Acid: either DNA or RNA (not both)
Proteins: few (cells have many)
Lipoprotein Membrane: envelope present in some (cells all have membranes)
Ribosomes: absent
Mitochondria: absent
Energy/ATP production: None
Enzymes: none or few

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3
Q

Non Enveloped

A

dsDNA: papovaviridae, adencoviridae, adenovirus
dsRNA: reoviridae
ssRNA: picornaviridae and calicivirus
ssDNA: parvoviridae

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4
Q

Enveloped

A

dsDNA: poxviridae, herpesviridae, hepadnaviridiae
ssRNA: paramyxoviridae, orthomyxoviridae, rhabdoviridae, retroviridae, arenaviridae, coronaviridae, bunyaviridae, togavirdae (Rubella), and flaviviridae

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5
Q

Viral Shape, Size, and Envelope

A

Size of viruses can vary- bacteriophage MS2 size and can reach a size as big as Chlamydia
Compared to E.coli, viruses are small
Piconavirus: have RNA as genome and very tightly packed because small
Largest virus (Poxvirus) is as large as Chlamydia but much smaller than E. coli

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6
Q

Viral Structure: Naked and Enveloped

A

We differentiate enveloped vs. non enveloped
Bacteriophage: capsid with nucleic acid to be injected into the host bacteria; naked/no envelope; the only thing that enters the cell is the DNA/RNA
Human viruses: they enter their capsid protein and nucleic acid; removal of the protein capsid and then freeing of the nucleic acid for reproduction happen within the host
Glycoprotein membrane: allows the glycoproteins to act as receptors that enable the virus to bind/attach to the host cell when it is going to infect it

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7
Q

Classification of Viruses

A

Several systems for classification of viruses have been used in the past
Most of these have been based on: viral disease, symptoms, and mode of transmission
In 1966, the International Committee on the nomenclature of Viruses was formed. Criteria for classification: mucleic acid type, composition, and size, virus morphology, serological cross-reactivity of group antigens

Morphology, physicochemical properties, genome properties, virus protein properties, biologic properties, antigenic properties

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8
Q

Morphology of Viruses

A

Size
Shape
Symmetry
Presence or absence of peplomers, which are virus-encoded glycoproteins inserted onto virus envelope
Presence or absence of envelope (membrane)

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9
Q

Physiochemical Properties

A
Molecular mass
Density
pH stability
Thermal stability
Susceptibility to physical and chemical agents such as ether and detergents
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10
Q

Genome Properties

A

Nucleic acid: DNA or RNA; ss or ds; linear or circular (linear is most common)
Size and type of genome
Sense: positive or negative
Segments (e.g., influenza)

Special features: 5’-terminal cap, 5’-terminal covalently linked protein, 3’-terminal poly[A] trail
Retroviruses contain RT (reverse transcriptase)
Capping enzymes to modify viral mRNA at their 5’ end by adding 7- methylguanosine
Polyadenylation of the 3’ end of viral mRNA
Virally coded enzymes: protein kinases, phosphatases, endonucleases, and RNAses

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11
Q

Virus Protein Properties

A
Number
Size
Functional activities
Amino acid sequence
Modifications (glycosylation)
Functional activities (transcriptase, RT, neuraminidase, fusion activities)
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12
Q

Biologic Properties

A

Natural host range: mode of transmission, vector relationship, pathogenicity, tissue tropism
Antigenic properties: serologic relationship with the host

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13
Q

Universal System of Virus Taxonomy

A

Families (morphology, genome structure, and strategies of replication).
Suffix “-viridae”
Genera (subdivision): based on physicochemical, serology, cytopathology, or epidemiology.

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14
Q

Viral Architecture

A
Three groups:
Icosahedral symmetry: has 20 faces (e.g., adenoviruses)
Helical symmetry (e.g., orthomyxoviruses)
Complex structure (e.g., poxviruses): has two membranes, one on the outside and one on the core with nucleic acid (DNA); outside one has the lateral bodies
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15
Q

Capsid vs. Nucleocapsid vs. Envelope

A

Capsid: protein shell, or coat. Encloses the nucleic acid genome
Nucleocapsid: protein-nucleic acid complex
Enveloped virus in addition to capsid, there is a membrane that surrounds the whole structure; membrane is biological composed of phospholipids with spikes
Outer Shell/Envelope:
1. Protects genome
2. Aids in the process of entry into the cell
3. Packages enzymes essential for the early
steps of the infectious process

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16
Q

Icosahedral Capsid Symmetry: No Envelope

A

Papillomaviruses/Papovavirus, Parvovirus, Adenovirus
Two key components:
1. Central core (the genome)
2. Outer shell of protein known as the capsid (made of proteins)
The capsid of each virus is an aggregation of morphologic units known as capsomeres
The core and capsid are known as the nucleocapsid

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17
Q

Icosahedral Capsid Symmetry with Envelope

A

Rubellavirus/Togavirus, Herpes, and HepB
Nucleocapsid is wrapped in an outer envelope
Between the nucleocapsid and envelope is the matrix protein
The viral envelop is derived from the membrane of the host cell
The viral envelope proteins generally appear as spikes known as peplomers made of glycoproteins
Envelope can help with cell attachment, but also a vaccine target

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18
Q

Helical Capsid Symmetry & Envelope

A

Influenzavirus
The capsid proteins are aggregated around the viral genome as a flexible hollow tube
The coiled nucleocapsid is wrapped in an envelope to form a virion

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19
Q

Virus With a Complex Symmetry

A

Smallpox/Poxvirus
The structure is much more complex
Features: an external envelope, complex layer of tubular structure, an internal structure made of a DNA-containing core and lateral bodies
Lateral bodies contain various enzymes essential for virus replication
Viruses with this morphology are among the largest of all viruses

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20
Q

DNA Viruses (6): Naked vs. Enveloped

A
Hepatitis B: enveloped
Herpesviruses: enveloped
Poxviruses: enveloped
Papovaviruses: naked
Parvoviruses: naked
Adenoviruses: naked
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21
Q

RNA Viruses (5): Naked vs. Enveloped

A
Picornaviruses: naked
Caliciviruses: naked
Arenaviruses: enveloped
Orthomyxoviruses: enveloped, segmented genome, 8 ss linear fragments
Paramyxoviruses: enveloped
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22
Q

RNA to DNA Viruses

A

Retroviruses (ssRNA)

Hepadnaviruses (dsDNA)

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23
Q

Segmented Genome

A

Viral genome: fragmented into two or more nucleic acid molecules; all fragments must be present in order to cause infection

Isocapsidic virus: all fragments of segmented genome located in the same virion like the influenza virus

Heterocapsidic virus: each fragment packaged in a different virion, and successful infection requires that at least one RNA of each type enters host cell
example: alfalfa mosaic virus with 4 different RNA segments

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24
Q

Arboviruses (Arthropod-borne)

A

Not a family of viruses, just all of them are spread by the bites of mosquitoes, ticks, or sandflies
Bunyaviruses
Flaviviruses
Togaviruses

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25
Enteric viruses
``` Infect the GI tract; may cause local or systemic infection, with or without GI symptoms; not a family of viruses Adenoviruses Caliciviruses Picornaviruses Rotaviruses ```
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Hepatitis viruses
Infects the liver Hepatitis A, B, C, D, E, G not a family, classification by transmission
27
Sexually Transmitted viruses
Spread by sexual contact; may cause local or systemic infection; not a family Papillomaviruses Retroviruses Herpes
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Respiratory viruses
``` Generally cause upper respiratory tract disease, some infect the lungs; not a family Some adenoviruses Coronaviruses Orthomyxoviruses Paramyxoviruses Rhinoviruses ```
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Poxviridae
Smallpox, vaccinia virus, variola, molluscum contagiosum linear dsDNA, has polymerase, replication in cytoplasm, enveloped DNA virus family
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Herpesviridae
HSV-1, HSV-2, varicella-zoster (VZV), Epstein-Barr virus (EBV), cytomegalovirus (CMV), human herpes viruses 6, 7, and 8 linear dsDNA, does not have its own polymerase, replication and assembly in the nucleus, enveloped with nuclear membrane DNA virus family
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Adenoviridae
Adenovirus linear dsDNA, does not have its own polymerase, replication in the nucleus, and naked DNA virus family
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Hepadenaviridae
Hepatitis B virus (HBV) circular ds DNA, has a polymerase, replication in the nucleus via a RNA intermediate, enveloped DNA virus family
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Papoviridae
JC virus, BK virus, SV40, papilloma virus, polyoma circular dsDNA, does not have its own polymerase, replication in the nucleus, and naked DNA virus family
34
Parvoviridae
Parvovirus B19 ssDNA, does not have its own polymerase, replication in the nucleus, and naked DNA virus family
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Paramyxoviridae
Parainfluenza virus, measles, mumps, respiratory syncytial virus (RSV) RNA virus family
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Orthomyxoviridae
Influenza virus types A, B, and C | RNA virus family
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Arenaviridae
Lassa fever virus, lymphocytic choriomeningitis virus | RNA virus family
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Rhabdoviridae
Rabies virus, vesicular stomatitis virus | RNA virus family
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Filoviridae
Ebola virus, Marburg virus | RNA virus family
40
Bunyaviridae
California encephalitis virus, Hanta virus, hemorrhagic fever virus RNA virus family
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Retroviridae
HIV, human T cell leukemia virus | RNA virus family
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Reoviridae
Rotavirus, Colorado tick fever virus | RNA virus family
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Picornaviridae
Rhinovirus, poliovirus, echoviruses, coxsackie virus | RNA virus family
44
Togaviridae
Rubella virus, equine encephalitis viruses (eastern, western, and Venezuelan) Ross River virus RNA virus family
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Flaviviridae
Yellow fever virus, dengue virus, St. Louis encephalitis, Hep C, West Nile RNA virus family
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Caliciviridae
Norwalk virus | RNA virus family
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Replication
1. Attachment 2. Entry (penetration) 3. Uncoating 4. Macromolecular synthesis: genome replication and protein synthesis 5. Assembly 6. Budding 7. Release via lysis of the host cell Stages of life of virus- take advantage to make drugs Best to capture virus at the stage before it enters the cell – Ab specific Ag that we know if present on the surface of the virus then neutralized Also target receptors on host cells that can be used for the virus; can’t make a drug for CD4 receptor for HIV because the drug will do the same thing as the virus and kill the T cells = bad
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Lytic & Lysogenic Cycle
Lytic Pathway: In lysis, the host cell's membrane is damaged and the cytoplasm is able to leak out. The cell dies rapidly, releasing virus particles Lysogenic Pathway: The lysogenic path is one of several temperate pathways in which the host cell is not killed outright, but is occupied by the virus and used as a factory for replicating the viral genes.. The viral infection enters a latent period during this process, but eventually undergoes the lytic process
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Viral Replication and Drug Targets
Recognition & Attachment are targeted & blocked by antibody and receptor antagonists Uncoating: Amantadine, Arildone, Rimantadine, Tromantadine Transcription: Interferon and Antisense oligos Replication: Nucleoside analogs and Phosphonoformate Assembly: Protease inhibitors
50
Steps to Viral Disease
Acquisition (entry into the body): inhalation (most common), skin, sexual transmission, oral-fecal route (GI), hematogenous (blood) Initiation of infection: viral recognition of receptor/replication and dissemination Incubation Prodrome (symptom or set of symptoms that appears shortly before an acute attack of illness; Greek "running ahead of“); pathogenesis with signs and symptoms Convalescence/recovery
51
Viral Pathogenesis
Abortive infection (nonproductive infection): the viral infection of a cell in which viral components may be synthesized without the production of infective viruses; infection without causing disease Lytic infection: infection of a bacterium by a bacteriophage with subsequent production of more phage particles and lysis, or dissolution, of the cell; the viruses responsible are commonly called virulent phages; responsible for acute infections Persistent infection: chronic (non-lytic, productive), latent, recurrent. transforming (oncogenic); shows signs every now and then
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Oncogenic Pathogenesis
Oncogenic viruses can cause 1. Transformation causing immortalization of cells 2. Uninhibited out-of-control growth 3. Loss of contact inhibition causing growth in 3-dimensional mass 4. Change in cellular morphology 5. Appearance of new surface antigens Different oncogenic viruses have different means by which they cause transformation: Providing growth stimulating genes: growth factors Interfere with tumor suppressor genes: loss of control Inhibiting cell death by deregulating apoptosis enzymes
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Oncogenic Viruses
Epstein-Barr virus: basopharyngeal carcinoma, Burkitt lymphoma (HPV), thymic carcinoma Hepatitis B virus: primary hepatocellular carcinoma Hepatitis C virus: primary hepatocellular carcinoma Human papilloma virus: cervical cancer Human T cell Leukemia virus: Leukemia/lymphoma
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Characteristics of DNA Viruses
DNA viruses have the following characteristics 1. Icosahedral symmetry: except pox virus with its complex symmetry 2. Double stranded DNA: except parvovirus with ssDNA 3. DNA replication in the nucleus: except poxvirus because it replicates in the cytoplasm
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DNA Virus Life Cycle
Attachment & penetration by fusion Latent phase: immediate early protein synthesis Active replication: early protein synthesis & genome replication Late Protein synthesis: structural proteins Assembly and release by exocytosis
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Parvoviridae Details
Parvovirus B19: naked, ssDNA, erythema infectiosum/ 5th disease/ slapped cheek fever; mostly in children Pathogenesis: virus infects immature RBCs (still has nucleus) causing an aplastic crisis in sickle cell patients Transmission: respiratory aerosols, maternal to fetal Clinical Syndromes: mild febrile disease, facial rash, lacy body rash, arthritis in adults
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Six Pediatric Diseases
1st: rubeola, measles via the measles virus 2nd: scarlet fever via streptococcus pyogenes 3rd: rubella, german measles via rubella virus 4th: staphylococcal scalded skin syndrome via staphylococcus aureus (exfoliative toxin producers) 5th: erythema infectiosum via parvovirus B19 6th: roseola infantum via HHV6-B/HHV7 1,3,5,6 = viral 2,4 = bacterial
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Papovaviridae Details
Human papilloma virus: common warts like plantar on the foot sole, painful and flat warts on face and hands in children and young adults, genital warts Condyloma acuminatum: STD affecting > 20 millions Laryngeal: young children and adults Structure: dsDNA, naked ``` Pathogenesis: enter through breaks in the skin or mucous membranes, 3-4 months to develop Oncogenic potential (E6 binds to p53, E7 binds to Rb) ``` Epidemiology/transmission: asymptomatic shedding, direct contact, sexual contact, birth, chewing
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HPV: More Serious Diseases
Head and neck tumors: serotypes 6 & 11 most common Anogenital warts Cervical cancer: serotypes 16 & 18; protective HPV vaccine for young girls Treatment: spontaneous regression of benign warts possible, cryocautery (liquid nitrogen or dry ice), electrocautery, laser, chemical treatment, interferon, surgical removal
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Adenoviridae Details
Adenovirus Structure: hexahedral with dsDNA, nonenveloped with hexons and penton fibers Disease pathogenesis: infection of epithelial cells lining the oropharynx, respiratory or GI tract; infections could be lytic, latent or transforming/oncogenic Transmission: fecal-oral route, fingers, fomites, swimming pools, person to person transmission, crowds such as classrooms and military caserne
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Adenovirus Clinical Symptoms
Pharyngitis (with pink eye)- mimics strep throat Acute respiratory tract disease with fever, cough, pharyngitis, cervical adenitis common among children and military recruits; incubation period is 5-8 days Other respiratory tract disease: colds, laryngitis, croup, bronchiolitis, pertussis-like syndrome and viral pneumonia Gastrointestinal disease: diarrhea Conjunctivitis and epidemic keratoconjunctivitis: swimming pools, shipyard workers, dust and debris Acute hemorrhagic cystitis: more common in boys Treatment: none/supportive with cold compresses and topical vasoconstrictors to provide symptomatic relief Topical antibiotics are rarely necessary, because secondary bacterial infection is uncommon Vaccine: Oral, live, non-attenuated virus- in the military Gene therapy: CF, SCID, cancer
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Herpesviridae
Herpes simplex virus = Human herpes virus HHV-1 to HHV-8; large enveloped dsDNA viruses HSV-1 and HSV-2 are the original herpes simplex viruses Direct contact- sexual, other intimate Enter in the mucous membranes or through skin breaks Virus replicates in cells at base of lesion Infects the innervating neuron and travels to the ganglion- trigeminal ganglia for HSV-1 and sacral for HSV-2 Virus then returns to the initial site of infection They are cause of severe pain; cold sores around the face/mouth and genital because they affect the nerves in the tissue = painful
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Human Herpesviridae Infections
HHV-1: herpes simplex 1; oral/genital, but predominantly oral/facial HHV-2: herpes simplex 2; oral/genital, but predominantly genital HHV-3: Varicella zoster virus (VZV); chicken pox or shingles HHV-4: Epstein Barr Virus (EBV) or lymphocryptovirus; mononucleosis, Burkitt's lymphoma, CNS lymphoma in AIDS patients, post-transplant lymphoproliferative syndrome, nasopharyngeal carcinoma HHV-5: Cytomegalovirus (CMV); mononucleosis like syndrome, retinitis, etc. HHV-6/7: Roseolovirus; 6th disease HHV-8: Kaposi's sarcoma-associated herpes virus/type of rhadinovirus; Kaposi's sarcoma, primary effusion lymphoma, some types of multicentric Castleman's disease
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HHV-1 and HHV-2
Transmission is via saliva, vaginal secretions, vesicles’ fluid (cold sore) Both can cause oral and genital lesions HHV-1: most common, more oral by mouth to skin contact, kissing, sharing drinking glasses, utensils and toothbrushes HHV-2: STD that affects genitals, anal & perianal, oropharynx 20% of persons 12 years of age or older nationwide are infected with HSV-2 Neonate infection could be lethal
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HHV-1 and HHV-2 Clinical Syndromes
Usually benign manifestations, recurrent, clear vesicle, erythematous base Primary herpes: gingivostomatitis and recurrent as fever blisters Herpes pharyngitis Herpetic keratitis Herpetic whitlow: PAINFUL Herpes gladiatorum (HG): wrestling Genital herpes: may be asymptomatic, painful lesions Herpes encephalitis: mainly HHV-1 Congenital herpes
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Recurrence of HHV-1 and HHV-2
HSV stay dormant in the nerve cell body / ganglion: HSV-1 resides in the trigeminal ganglion HSV-2 resides in the sacral ganglia Reactivation occurs from these locations to the respective innervated body areas This is why: dormant virus from the trigeminal ganglion (oral or facial area) reactivates in the oral or facial region, whereas the dormant virus from the sacral ganglion (lower back/spine area) reactivate to the genital area or the buttock
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HHV-1 and HHV-2 Treatment
Herpes drugs are nucleotide analogs, viral DNA polymerase inhibitors, Acyclovir (ACV), Valacyclovir, Penciclovir, Famciclovir Viral thymidine kinase phosphorylates ACV so cellular enzymes add 2 more PO4 groups to become acyclo-GTP then activated acyclo-GTP incorporates into growing DNA strand and synthesis inhibited Requirement of viral thymidine kinase for activation makes acyclovir specific, effective, without side effects on the host, useful for prophylaxis Acyclovir resistance as a result of viral TK mutation causing no ACV activation Drugs used to treat herpes keratitis and its complicated form dendritic corneal ulcer: Trifluridine, Penciclovir, Acyclovir
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HSV Neonatal Infection
Maternal transmission of HSV-2 occurs: during delivery (85% of cases) in uterus, or first few weeks after birth HSV-2 disease manifestations: skin eye & mouth disease (SEM), CNS disease: encephalitis &/or meningitis, w or w/o SEM, disseminated disease causes death
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Varicella Zoster Virus (HHV-3; VZV): Pathogenesis
Viruses replicated in respiratory tract, spread to the blood, then to the lymphatics After a secondary viremia, the virus spreads to the skin Dermal manifestations: vesiculopustular rash Fever Latent in dorsal root ganglia Spreads along neural pathways to the skin Effects single dermatome causing zoster (shingles) Cause of chicken pox and shingles that affects adults Anyone who had chicken pox as a child – the virus is still in the body; at old age when there is weak immune system and stressed the virus can become active Very painful sores on the skin
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Epidemiology of VZV
Extremely contagious Infection exceeding 90% in susceptible households Spread via respiratory (aerosols) route and contact with skin vesicles Contagious even before symptoms appear and continues during symptomatic disease Up to 20% will have reactivation as zoster in old age Viable virus in zoster, which can be transmitted to children
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Varicella
Chickenpox Fever, maculopapular rash, 14d incubation rash will turn vesicular within hours Successive crops of lesions 3-5 days Rash is more severe on trunk, but present on extremities, lesions on scalp, mouth, conjunctivae and vagina Lesions are itchy so scratching can cause super infection, especially if infected with strep pyogenes, which can cause necrotizing fasciitis More severe in adults with interstitial pneumonia Zoster/Shingles: severe pain in the nerve precedes lesions and limited to one dermatome
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VZV Treatment
Children: none/supportive Adults and Immunosuppressed: Acyclovir, Famciclovir, Valcyclovir Immunosuppressed: immunization with VZV-Ig VZV vaccine: live, attenuated Children vaccinated after 12 months of age